Second-seeded American Isner notched his second ATP title in as many weeks after lifting the trophy in Newport last week.
Atlanta was the perfect place for him to keep the momentum going. Isner, who has reached the final in seven of eight editions of the tournament, added a fourth title to those he won in 2013, 2014 and 2015.
Harrison, seeded fourth, was denied a second career ATP title, to go with his victory in Memphis in February.
Never dreamed of becoming Wimbledon legend: Federer
"There wasn't much that separated us at all," said Isner. "So I'm happy to win that match in straight sets ... very happy to win today."
Both players held serve throughout the opening set to force the tiebreaker, in which Isner faced a set-point at 5-6 but saved it with a booming serve.
He then converted a set-point of his own at 7-6 with a forehand winner.
Title for Federer, tears for Cilic in one-sided Wimbledon final
Harrison ended Isner's run of 75 straight service holds — dating back to last week's Newport tournament -- when he broke for a 2-0 lead in the second set.
But Isner broke back immediately, and they held serve to another tiebreaker.
Harrison made Isner work for it, saving a match point with a forehand winner before giving himself a set-point at 7-6.
Isner responded with an ace, and went on to seal the victory his second match point with a forehand winner up the line.
COMMENTS
Comments are moderated and generally will be posted if they are on-topic and not abusive.
For more information, please see our Comments FAQ